Having done a quick pencil sketch of a site layout, I just brought up InDesign, used Layout > Create Guides to snap on a quick 12-grid (which is what our site is based on), and began comping up the divs.
The result is that I’ve saved myself several frustrating iterations of moving headers inside and outside wrappers, finding what needs to go all the way across and what needs to be inside.
Big fan. I think I’ll do this lots in the future.